Influence of hypertension and hypoxemia on arterial biochemistry and morphology in swine

Abstract

Eleven miniature swine were exposed to a simulated altitude of 5,490 m for 4 weeks and eleven control animals were maintained at the laboratory altitude of 1,524 m to study the effects of hypoxemia and hypertension on the biochemistry and morphology of the arterial wall. In comparison to controls, swine at 5,490 m had normal levels of plasma lipid and systemic arterial pressure, were extremely hypoxemic, and developed severe pulmonary hypertension. Enzyme analyses revealed increased activities of nucleotide pyrophosphatese and lactate dehydrogenase and decreased activity of succinate dehydrogenase in the media of both the hypoxic/normotensive aorta and hypoxic/hypertensive pulmonary artery. Electron microscopy indicated that smooth muscle cells in the mid-media of both vessels contained swollen mitochondria, focal areas of cytoplasmic degeneration, and lipid droplets. While there were no discernible alterations of aortic morphology at the light-microscopic level, the hypoxic/hypertensive pulmonary artery underwent a diffuse intimal, medial, and adventitial thickening. The thickening was characterized by an accumulation of fibrous protein and an increased amount of ground substance. Smooth muscle cells in the inner media of the thickened pulmonary artery contained an increased amount of granular endoplasmic reticulum and a prominent Golgi apparatus. The intima-media levels of cholesterol and free fatty acid were elevated in the hypoxic/hypertensive pulmonary artery, but not in the hypoxic/normotensive aorta. This study demonstrated that 4 weeks of severe hypoxemia in miniature swine elicited measurable changes in the enzymatic activity of the aortic and pulmonary arterial walls. In conjunction with alterations of glycolytic and oxidative enzyme activities that were indicative of decreased oxidative metabolism, ultrastructural changes demonstrated abnormalities of the metabolic machinery. In the absence of additional stresses, the metabolic abnormalities did not lead to the gross accumulation of lipid by the aortic wall within the 4-week period of study. However, when the arterial wall was subjected to the combined stresses of hypoxia and hypertension (as was the hypoxic/hypertensive pulmonary artery), the resulting metabolic and morphologic alterations were sufficiently pathogenetic to elicit vascular lipid accumulation within 4 weeks.